4-(hydroxyanilino)-2-(5-nitro-2-furyl)quinazolines



United States Patent ABSTRACT OF THE DISCLOSURE Novel 4 (hydroxyanilino)-2-(5-nitro-2-furyl)quinazolines are provided which possess exceptional antibacterial potency against microorganisms, particularly those of importance in veterinary medicine and especially against those associated with bovine mastitis.

This invention is concerned with chemical compounds and aims to provide novel 4-(hydroxyanilino)-2-(5-nitro- 2-furyl)quinazolines of the formula:

O rNj wherein R is hydroxy. These compounds possess a very high order of antibacterial activity particularly in respect to those organisms prevalent in the veterinary field.

It is known from US. Pat. No. 3,324,122 that certain 4-substituted-2-(5-nitro-2-fury1)quinazolines are antibacterial agents having a broad antibacterial spectrum and that the compounds of that patent having a 4-amino substituent also possess activity in suppressing in vivo lethal infections provoked by Staphylococcus aureus in animals.

Surprisingly the compounds of this invention do not possess such in vivo activity. They do, however, possess an unexpectedly greater in vitro antibacterial potency particularly toward those organisms such as Streptococcus agalactiole and Staphylococcus aureus, commonly occurring pathogens in bovine mastitis; Salmonella typhimurium and Escherichia coli, organisms of concern in calf enteritis; Pasturella multocida, a causative agent in fowl cholera; and Moraxella bovis, frequently associated with infectious keratoconjunctivitis in cattle.

The following table is representative of the antibacterial effect of the ortho-, meta-, and parahydroxyanilino-Z-(S- nitro-2-furyl) quinazolines of this invention:

3,542,784 Patented Nov. 24, 1970 "ice The amount of a compound of this invention to be incorporated in such compositions ranges from 0.1-1.0 percent by weight thereof, such concentration being sufiicient to achieve the effect desired.

The compounds of this invention are rather readily prepared. The method which is currently preferred consists in reacting the appropriate hydroxyaniline with a 4-halo-2- (5-nitro-2-furyl)quinazoline in the presence of a solvent inert to the reactants and preferably under the influence of heat to hasten the reaction.

In order that this invention may be readily available to and understood by those skilled in the art the following examples of the preparation of the compounds thereof are appended.

EXAMPLE I 4- (o-hydroxyanilino -2- 5-nitro-2-furyl) quinazoline A 1 1., three-neck flask, fitted with a stirrer, was charged with 35 g. (0.127 mole) of 4-chloro-2-(S-nitro-Z-furyl) quinazoline and 28.5 g. (0.26 mole) of o-hydroxyaniline in 500 ml. of dimethylformamide. The solution was heated on a steam bath for 2 hours. The solution was diluted with water until a solid began to separate. The mixture was cooled; the crude product was collected by filtration, and recrystallized from dilute aqueous dimethylformamide. The product separated as orange platelets melting at 275 dec. (corn) in a yield of 35 g. (70.5%).

Analysis.--Calcd. for C H N O (percent): C, 62.07; H, 3.47; N, 16.09. Found (percent): C, 61.89; H, 3.57; N, 15.90.

EXAMPLE II 4-(m-hydroxyanilino)-2-(5-nitro-2-furyl)quinazoline A 1 1., three-neck flask, fitted with a stirrer, was charged with 35 g. (0.127 mole) of 4-chloro-2-(5-nitro-2-furyl) quinazoline and 28.5 g. (0.26 mole) of m-hydroxyaniline in 500 ml. of dimethylformamide. The solution was heated on a steam bath, with stirring, for 2 hours. The solution was diluted with water until a solid began to separate. The mixture was cooled; the crude product was collected by filtration, and recrystallized from dilute aqueous dimethylformamide. The product separated as yellow needles melt ing at 284 dec. (corr.) in a yield of 39 g. (88% Analysis.--Calcd. for C H N O (percent): C, 62.07; H, 3.47; N, 16.09. Found (percent): C, 62.05; H, 3.54; N, 16.10.

EXAMPLE HI 4- (p-hydroxyanilino -2- (5-nitro-2-furyl) quinazoline A solution of 30.2 g. (0.11 mole) of 4-chloro-2-(5-nitro- 2-furyl)quinazoline and 27.2 g. (0.25 mole) of p-aminophenol in 500 ml. of dimethylformamide was heated on a steam bath for 2 hours. The solution was diluted with water until a dark solid had separated. The mixture was cooled. The solid was collected by filtration and recrystallized from dilute aqueous dimethylformamide. The

Minimum inhibitory cone. in meg/ml.

S. agalactiae S. aureus S. typhimurium Compound:

ortho- 1. 0 0. 03 0. meta- 0. 06 0. 03 1. para- 0. 015 0. 06 0.

E. 0011' P. mullocida M. bovis product, melting at 286288 dec. (com), was collected by filtration in a yield of 35 g. (91.5%

Analysis.-Calcd. for C H N O (percent): C, 62.07; H, 3.47; N, 16.09. Found (percent): C, 62.01; H, 3.58; N, 15.78.

What is claimed is:

1. A compound of the formula:

wherein R is hydroxy.

2. The compound 4-(o-hydroxyanilino)-2-(5-nitr0-2- furyl) quinazoline.

3. The compound 4-(m-hydroxyanilino)-2-(5-nitro-2- furyl)quinazoline.

3,238,208 3/1966 Gems et a1 260-2564 3,324,122 6/1967 Burch 260-2564 ALEX MAZEL, Primary Examiner 10 R. J. GALLAGHER, Assistant Examiner US. Cl. X.R. 

